PMID- 34724197 OWN - NLM STAT- MEDLINE DCOM- 20220309 LR - 20230310 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 128 IP - 5 DP - 2022 Mar 1 TI - Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit. PG - 975-983 LID - 10.1002/cncr.34004 [doi] AB - BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit. CI - (c) 2021 American Cancer Society. FAU - Patel, Anisha B AU - Patel AB AUID- ORCID: 0000-0002-5372-784X AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. AD - McGovern Medical School, The University of Texas Health Science Center, Houston, Texas. FAU - Farooq, Sahira AU - Farooq S AD - McGovern Medical School, The University of Texas Health Science Center, Houston, Texas. FAU - Welborn, Macartney AU - Welborn M AD - Department of Dermatology, University of Florida, Gainesville, Florida. FAU - Amaria, Rodabe N AU - Amaria RN AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Chon, Susan Y AU - Chon SY AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Diab, Adi AU - Diab A AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Glitza Oliva, Isabella C AU - Glitza Oliva IC AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Huen, Auris O AU - Huen AO AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Li, Shirley Q AU - Li SQ AD - Baylor College of Medicine, Houston, Texas. FAU - Nelson, Kelly C AU - Nelson KC AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. AD - McGovern Medical School, The University of Texas Health Science Center, Houston, Texas. FAU - Pacha, Omar AU - Pacha O AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Patel, Sapna P AU - Patel SP AUID- ORCID: 0000-0003-1339-1517 AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Rapini, Ronald P AU - Rapini RP AD - Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas. AD - McGovern Medical School, The University of Texas Health Science Center, Houston, Texas. FAU - Tawbi, Hussein A AU - Tawbi HA AUID- ORCID: 0000-0003-1942-851X AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Wong, Michael K AU - Wong MK AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - McQuade, Jennifer AU - McQuade J AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Davies, Michael A AU - Davies MA AD - Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Haydu, Lauren E AU - Haydu LE AD - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20211101 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Ipilimumab) RN - 31YO63LBSN (Nivolumab) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal, Humanized MH - Humans MH - *Immunotherapy/adverse effects MH - Incidence MH - Ipilimumab MH - *Melanoma/pathology MH - Nivolumab MH - Skin Diseases/*chemically induced MH - *Skin Neoplasms/pathology OTO - NOTNLM OT - anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA4) OT - anti-programmed death 1 (anti-PD1) OT - cutaneous adverse events OT - immune checkpoint inhibitors OT - ipilimumab OT - melanoma OT - nivolumab OT - pembrolizumab EDAT- 2021/11/02 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/11/01 16:57 PHST- 2021/09/01 00:00 [revised] PHST- 2021/07/17 00:00 [received] PHST- 2021/09/28 00:00 [accepted] PHST- 2021/11/02 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/11/01 16:57 [entrez] AID - 10.1002/cncr.34004 [doi] PST - ppublish SO - Cancer. 2022 Mar 1;128(5):975-983. doi: 10.1002/cncr.34004. Epub 2021 Nov 1.